1. Field of the Invention
The present invention relates generally to vaccines. More particularly, it concerns compositions of antigens and adjuvants, and methods of their use. In specific embodiments, the invention concerns compositions comprising virus-like particle (“VLF”) antigens and Murabutide.
2. Description of Related Art
Virus-like particles (“VLPs”) typically consist of assembled protein subunits of a pathogenic virus that are capable of inducing an anti-viral (protective or therapeutic) immune response when administered to a subject, but are devoid of some or all of the nucleic acids necessary for viral replication. Thus, VLPs embody the best features of immunization with live or attenuated viruses, namely the induction of a relevant immune response, but lack the potential for causing disease because of the inability of the VLP to replicate in the subject.
There are many examples of VLPs and VLP-vaccine technology, and the use of VLPs as a vaccine platform finds particular value in mucosal immunization against viral pathogens. Examples of target diseases that can be treated by VLP immunization (prophylactically), or which might be ameliorated in terms of severity by VLP treatment after viral infection (therapeutically) include influenza (“flu”) virus, hepatitis viruses, caliciviruses and essentially any virus whose capsid subunits can assemble into stable VLP after production.
While the immunogenicity and potential clinical benefit of VLPs have been demonstrated, as with any vaccine antigen, VLP immunogenicity might not always be sufficiently strong to mount a protective response—that is, an immune response might be induced by vaccination with a VLP antigen, but the strength, type and/or duration of the response might not be sufficiently robust to fend off disease upon a subject's exposure to the viral pathogen. Adjuvants are often used in conjunction with vaccine antigens to correct the inherent deficiencies of weak antigens. Adjuvants include molecules in many chemical and biological categories, with equally diverse modes of action. Modes of action of adjuvants include immunomodulation, antigen presentation enhancement, cytotoxic T-lymphocyte (CTL) induction, antigen targeting promotion, and depot generation. Examples of vaccine adjuvants include those that trap the antigen in a depot, such as alum, and enable immune system cells to sample and process the adjuvant over time, with an enhanced immune potentiating effect. Cytokines (cellular and immune regulatory molecules), such as granulocyte-macrophage colony stimulating factor (GM-CSF), have been used to cause a local inflammatory reaction to enhance exposure of immune cells to the antigen and to enhance the magnitude and duration of the immune response.
Presentation of a vaccine antigen, including VLP, through mucosal exposure (e.g. nasal, pulmonary, oral, vaginal) can lead to the development of mucosal immune protective effects, such that when a subject is exposed to a viral pathogen that gains entry through a mucosal surface the subject can be protected by this mode of vaccination. As summarized above, mucosal vaccination through exposure to an antigen by itself might not lead to protective immunity, and adjuvants can be used to overcome this deficiency. However, the field of mucosal vaccination is relatively new, unlike the more typical routes of intramuscular and subcutaneous vaccine administration, for which typical adjuvants include those that form a depot such as alum or enhance local inflammatory effects, such as cytokines. Consequently, there is a great need for new appropriate, safe and effective mucosal vaccine adjuvants. The present invention addresses this challenge with technology for adjuvanting (potentiating) the immune response to antigens, such as VLPs.